RNF6 promotes gastric cancer progression by regulating CCNA1/CREBBP transcription
RNF6 promotes gastric cancer progression by regulating CCNA1/CREBBP transcription
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DOI：
10.1080/15384101.2023.2275899
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发表时间：
2023-11-01
期刊：
影响因子：
4.3
通讯作者：
Huang，Chen
中科院分区：
文献类型：
--
作者：
Jiang，Qiuyu;Miao，Jiyu;Huang，Chen
Ring finger protein 6（RNF 6）是E3泛素连接酶家族的成员。先前的研究已经报道RNF 6作为泛素连接酶参与胃癌（GC）的进展。然而，本研究发现RNF 6在GC的细胞核中具有明确的定位，表明其作用不同于泛素连接酶。进一步的染色质免疫沉淀测序（ChIP-seq）分析显示，RNF 6具有DNA结合和转录调控作用，并参与肿瘤细胞周期和凋亡等重要途径。细胞周期蛋白A1（CCNA 1）和CREB结合蛋白（CREBBP）是胃癌中RNF 6转录调控的下游靶点。RNF 6与CCNA 1/CREBBP的启动子区结合，并积极调节它们在GC细胞中的表达。沉默CCNA 1/CREBBP可部分逆转RNF 6过表达对胃癌细胞生物学功能的促进作用。我们的研究表明RNF 6通过调节CCNA 1/CREBBP的转录而促进胃癌的进展。
Ring finger protein 6 (RNF6) is a member of the E3 ubiquitin ligase family. Previous studies have reported the involvement of RNF6 as a ubiquitin ligase in the progression of gastric cancer (GC). However, this study found that RNF6 has a clear localization in the nucleus of GC, indicating a role other than ubiquitin ligase. Further chromatin immunoprecipitation sequencing (ChIP-seq) analysis revealed that RNF6 has DNA binding and transcriptional regulatory effects and is involved in important pathways such as tumor cell cycle and apoptosis. Cyclin A1 (CCNA1) and CREB binding protein (CREBBP) are downstream targets for RNF6 transcription regulation in GC. RNF6 binds to the promoter region of CCNA1/CREBBP and is actively regulating their expression in GC cells. Silencing CCNA1/CREBBP partially reversed the promoting effect of RNF6 overexpression on the biological function of GC cells. Our study suggests that RNF6 promotes the progression of GC by regulating CCNA1/CREBBP transcription.